The objective of the Specialized Cooperative Centers Program in Reproductive Research (SCCPRR) at the University of llinois is to conduct innovative basic and clinical research in the reproductive sciences. Four projects are proposed. 3rojects I and n focus on the etiology and pathophysiology of endometriosis while Projects HI and IV address important questions relating to decidualization and implantation in rodent models. Insights gained on the regulation of cell cycle, ipoptosis and metalloproteinases in these rodent models, however, will be directly applicable to understanding the jhysiology and pathobiology of human reproduction. Project I "Endometriosis in the Baboon" - will test the hypothesis hat the development of endometriosis occurs in two distinct phases. The data generated will determine if ovarian steroids are necessary to first establish the disease and if local steroid biosynthesis will maintain it. This project will also establish a direct link between endometriosis and aberrations in uterine receptivity. Project II "Hormone Action in indometriosis" - will test the hypothesis that progesterone resistance in endometriotic tissue disrupts the induction of the cey estradiol (E2) metabolizing enzyme 17/?-hydroxydehydrogenase (HSD) type 2. A major goal is to determine whether iberrations in nuclear receptor expression causing progesterone resistance and the absence of 17P-HSD-2 giving rise to increased tissue E2 levels are responsible for altered cell fate in endometriosis. Project PI "Cell Signaling and Gene Regulation in Decidual Development" will focus on the functional role of decidual-derived proteins. Using transgenic nice models, the role and regulation of cell cycle inhibitors, activin A and prolactin in the development and maintenance )f the decidua during pregnancy will be evaluated. Project IV "EMMPRIN Regulates Metalloproteinases in the Endometrium" tests the hypothesis that an inducer of metalloproteinases (EMMPRIN) that is secreted by uterine epithelial cells regulates metalloproteinase (MMP) production in the endometrium. These studies will focus on the importance of MMPs in implantation and determine if EMMPRIN expression is required for MMP production by ;ndometriotic tissue. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula md support 7 other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of he U54 application. The U54 Center at the University of Illinois will be established within a strong interactive and collegia! environment and in an institution that has a rich history in reproductive research.